EP1268400A2 - Procede de preparation d'ester de methyle d'acide n-butyryl-4-amino-3-methyl-benzoique et le nouveau compose n-(4-brome-2-methylphenyl)-butanamide - Google Patents

Procede de preparation d'ester de methyle d'acide n-butyryl-4-amino-3-methyl-benzoique et le nouveau compose n-(4-brome-2-methylphenyl)-butanamide

Info

Publication number
EP1268400A2
EP1268400A2 EP01933703A EP01933703A EP1268400A2 EP 1268400 A2 EP1268400 A2 EP 1268400A2 EP 01933703 A EP01933703 A EP 01933703A EP 01933703 A EP01933703 A EP 01933703A EP 1268400 A2 EP1268400 A2 EP 1268400A2
Authority
EP
European Patent Office
Prior art keywords
methyl
butanamide
methylphenyl
butyryl
bromo
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP01933703A
Other languages
German (de)
English (en)
Other versions
EP1268400B1 (fr
Inventor
Lars Rodefeld
Thomas Höpfner
Alexander Klausener
Horst Behre
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lanxess Deutschland GmbH
Original Assignee
Bayer AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer AG filed Critical Bayer AG
Publication of EP1268400A2 publication Critical patent/EP1268400A2/fr
Application granted granted Critical
Publication of EP1268400B1 publication Critical patent/EP1268400B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
    • C07C233/15—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups

Definitions

  • the present invention relates to an improved ner driving for the production of
  • biphenyl-2-carboxylic acid is a valuable angiotensin antagonist, especially a valuable angiotensin -II antagonist (see EP-A 502 314) This carboxylic acid is also called antagonist for short.
  • the compound (II) is then converted to the antagonist in further steps.
  • the required starting compound of the formula (I) can only be obtained in a disadvantageous manner.
  • the known process for the preparation of the compound (II) consists of four individual stages, the first stage (III) - (IV) being particularly disadvantageous because it requires long reaction times and it is only unselective and therefore low
  • Steps (VII) ⁇ (VIII) and (VIII) ⁇ (II) are particularly surprisingly advantageous because they deliver (VIII) and (II) in each case in yields of over 95%.
  • the first step of the process according to the invention the reaction of compound (VI) with butyryl chloride to give compound (VII), can be carried out, for example, by reacting compound (VI) in an inert solvent, e.g. submitted to an aromatic solvent such as chlorobenzene, toluene or xylene and then metered in butyric acid chloride at temperatures of, for example, 50 to 100.degree.
  • an inert solvent e.g. submitted to an aromatic solvent such as chlorobenzene, toluene or xylene
  • butyric acid chloride at temperatures of, for example, 50 to 100.degree.
  • the o-toluidine hydrochloride is also initially formed, which, if desired, can be converted completely to the amide by further heating.
  • the progress of the reaction can be followed by the formation of hydrogen chloride. To destroy any remaining
  • Residues of butyric acid chloride can be added to methanol. After cooling the reaction solution, the amide (VII) precipitates and can be e.g. isolate by filtration with a purity of generally over 98% and in yields of generally 92 to 95%.
  • the second step of the process according to the invention the bromination of compound (VII) to compound (VIII), can be carried out, for example, by initially introducing compound (VII) in acetic acid at 10 to 80 ° C., the 1 to 1.3 molar amount add elemental bromine together with further acetic acid, stir the mixture at 10 to 80 ° C for 20 minutes to 3 hours, then 0.5 to 5 times
  • the third step of the process according to the invention the conversion of compound (VIII) by reaction with carbon monoxide and methanol in the presence of a
  • Palladium catalyst for compound (II) can be carried out, for example, by placing the compound of formula (VIII) and a palladium catalyst in a pressure vessel, then adding a mixture of methanol, optionally one or more solvents other than methanol and a base, then at 90 to 160 ° C pressures 2 to 30 bar carbon monoxide and maintains this pressure until no more carbon monoxide is absorbed.
  • methanol can serve as a reactant and as a solvent.
  • organic solvents other than methanol can also be used.
  • Preferred additional organic solvents are hydrocarbons such as hexane, cyclohexane, heptane, benzene, toluene, the isomeric xylenes and their mixtures, chlorinated hydrocarbons such as chlorobenzene, dichlorobenzene, methylene chloride and hexochloroethane, nitriles such as acetonitrile, amides such as dimethylformamide and ethers such as dioxane and tetrahydrofuran.
  • the use of such solvents is advantageous if it increases the solubility of the carbon monoxide in the solution.
  • This reaction stage can then be carried out at relatively lower pressures, which is associated with less outlay in terms of equipment and safety, particularly on an industrial scale.
  • the triphenylphosphine component can also be used in excess.
  • Suitable bases are, for example, carbonates, hydrogen carbonates and acetates of alkali metals. However, preferred are primary, secondary and tertiary amines, in particular tri-C ⁇ -C ⁇ o-alkylamines. Based on 1 mol of compound (VIII), for example 0.9 to 5 mol, preferably 1.05 to 2 mol, of base can be used.
  • the compound (II) can be prepared in a 3-step process with good yields and can be obtained in good purities.
  • the yield in the process according to the invention is generally 90 to 95% over all 3 stages. This is a significant improvement in the accessibility to compound (II) and to the antagonists that can be prepared from compound (II).
  • One embodiment of the process according to the invention is a synthesis of (VIII) without intermediate isolation of the compound (VII). This is technically advantageous, since the intermediate insulation of a connection always requires additional units that slow down the process and are usually caused by insulation losses and residues, e.g. in mother liquors, reduce the yield.
  • the first step is how to produce the
  • Acetic acid and mixtures of acetic acid and water are particularly preferred.
  • Bromine is added directly to this reaction mixture at temperatures of 10 to 130 ° C., preferably 30 and 60 ° C. Based on one mole of compound (VII), 0.9 to 1.1 moles of bromine, preferably 1 to 1.05 moles, can be added.
  • This embodiment therefore also provides for only 0.45 to 0.95 mol of bromine to be used per 1 mol of compound (VII) and for the further bromination to be carried out in an amount in addition to 1 mol by reoxidizing hydrobromic acid with an oxidizing agent, preferably hydrogen peroxide ,
  • the bromination can also be carried out with hydrobromic acid, after the addition of which an oxidizing agent is added.
  • hydrobromic acid can be used as a solution in water.
  • bromides can also be used, preferably potassium bromide. Bromides can be used as such or in, for example, aqueous solution.
  • the compound of formula (VIII) is new.
  • the present invention therefore also relates to the compound of formula (VIII), i.e. N- (4-bromo-2-methylphenyl) butanamide.
  • reaction solution was then freed from the catalyst by boiling with activated carbon, and 500 ml of water were then added at 80.degree. At the same time, as much methanol as possible was removed by distillation. The product precipitated and was isolated by filtration. 73.4 g of colorless crystals (88% yield) were obtained in 99.5% purity.
  • the metering end is heated to reflux and stirred until the evolution of gas plus one hour of post-reaction time.
  • the mixture was then cooled to 70-75 ° C. 20 g of methanol were added and the mixture was stirred at 75 ° C. for 1 hour.
  • the mixture was heated (1-10 BOX) and 808 g of distillate were distilled off. Towards the end of the distillation

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
EP01933703A 2000-03-28 2001-03-15 Procede de preparation d'ester de methyle d'acide n-butyryl-4-amino-3-methyl-benzoique et le nouveau compose n-(4-brome-2-methylphenyl)-butanamide Expired - Lifetime EP1268400B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10015279 2000-03-28
DE10015279A DE10015279A1 (de) 2000-03-28 2000-03-28 Verfahren zur Herstellung von N-Butyryl-4-amino-3-methyl-benzoesäuremethylester und die neue Verbindung N-(4-Brom-2-methylphenyl)-butanamid
PCT/EP2001/002924 WO2001072690A2 (fr) 2000-03-28 2001-03-15 Procede de preparation d'ester de methyle d'acide n-butyryl-4-amino-3-methyl-benzoique et le nouveau compose n-(4-brome-2-methylphenyl)-butanamide

Publications (2)

Publication Number Publication Date
EP1268400A2 true EP1268400A2 (fr) 2003-01-02
EP1268400B1 EP1268400B1 (fr) 2004-08-11

Family

ID=7636623

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01933703A Expired - Lifetime EP1268400B1 (fr) 2000-03-28 2001-03-15 Procede de preparation d'ester de methyle d'acide n-butyryl-4-amino-3-methyl-benzoique et le nouveau compose n-(4-brome-2-methylphenyl)-butanamide

Country Status (9)

Country Link
US (2) US6620962B2 (fr)
EP (1) EP1268400B1 (fr)
JP (1) JP2003528846A (fr)
CN (1) CN1184194C (fr)
AT (1) ATE273270T1 (fr)
AU (1) AU2001260124A1 (fr)
DE (2) DE10015279A1 (fr)
ES (1) ES2227193T3 (fr)
WO (1) WO2001072690A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5001187A (en) * 1989-10-16 1991-03-19 Dow Corning Corporation Emulsions of silicone elastomer

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004009051A2 (fr) * 2002-07-18 2004-01-29 Quest International Services B.V. Ameliorations apportees ou associees a des compositions de parfum
CA2701522C (fr) * 2004-02-27 2012-05-15 Roger P. Jackson Ensemble d'instruments de reduction de tige d'implant orthopedique et methode associee

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW397819B (en) 1994-03-31 2000-07-11 Nihon Nohyaku Co Ltd A process for producing a substituted benzoyl fatty acid derivative

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0172690A2 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5001187A (en) * 1989-10-16 1991-03-19 Dow Corning Corporation Emulsions of silicone elastomer

Also Published As

Publication number Publication date
AU2001260124A1 (en) 2001-10-08
US20040030183A1 (en) 2004-02-12
US6620962B2 (en) 2003-09-16
CN1419535A (zh) 2003-05-21
ES2227193T3 (es) 2005-04-01
US20030065211A1 (en) 2003-04-03
EP1268400B1 (fr) 2004-08-11
DE50103229D1 (de) 2004-09-16
ATE273270T1 (de) 2004-08-15
WO2001072690A3 (fr) 2002-02-28
DE10015279A1 (de) 2001-10-04
JP2003528846A (ja) 2003-09-30
WO2001072690A2 (fr) 2001-10-04
CN1184194C (zh) 2005-01-12

Similar Documents

Publication Publication Date Title
DE2419970C3 (de) 3-<l-Pyrrolidinyl)-4-phenoxy-5sulfamoylbenzoesäure und Verfahren zu ihrer Herstellung
DE3010195C2 (fr)
DE1795841B2 (de) l-a'-Chlort-benzyl^-di-sec-butylamino-acetyl-pyiTol, seine Salze und Verfahren zu deren Herstellung
EP1669346A1 (fr) Procédé de préparation des dérivés d'esters d'acide carbamique
EP1268400B1 (fr) Procede de preparation d'ester de methyle d'acide n-butyryl-4-amino-3-methyl-benzoique et le nouveau compose n-(4-brome-2-methylphenyl)-butanamide
WO2007115685A1 (fr) Procédé pour préparer des biphénylamines par l'intermédiaire de vinylanilines
DE2501899B1 (de) Verfahren zur herstellung von 2- nitro-4,6-dichlor-5-methylphenol
EP0621262B1 (fr) Procédé de préparation d'esters très purs de l'acide 3-chloroanthranilique au départ de cet acide
EP0216324B1 (fr) Ester d'acides 4-alkoxy-3-pyrrolin-2-one-1-yl-acétiques et leur préparation
DE2263527C3 (de) 2,2-Disubstituierte Phenylacetonitril-Derivate, Verfahren zu ihrer Herstellung und deren Verwendung
DE3104643A1 (de) Verfahren zur herstellung von gegebenenfalls p-chlorsubstituiertem 2,6-diaminotoluol
EP0006180B1 (fr) 3-Phénoxybenzylidène-amines et 3-benzylbenzylidène-amines, procédé pour les préparer et leur utilisation pour préparer les aldéhydes correspondants
DE2614241A1 (de) Verfahren zur herstellung von acylcyaniden
EP1902042A1 (fr) Procede de preparation d'acide 3,4-dichloro-isothiazolcarboxylique
DE4408083C1 (de) Verfahren zur Herstellung von 4-Fluoralkoxyzimtsäurenitrilen
EP0152598A1 (fr) Cyanométhyl-(2-cyano-éthyl)-(3-hydroxy-propyl)-amine et son utilisation pour la production de 1-(3-hydroxy-propyl)-1,4-diazepan et 1,4-bis-[3-(3,4,5-triméthoxy-benzoyloxy)-propyl]-diazepan
AT376417B (de) Verfahren zur herstellung von phenylaethanolaminen und ihren salzen
DE3515094C2 (fr)
EP0811607A1 (fr) Procédé de nitrosation de composés à C-H- acides
AT380873B (de) Verfahren zur herstellung von 1-(4-isopropylthiophenyl)-2-n.octyl-amino -propanol, dessen saeureadditionssalzen und estern
DE2820575B2 (de) Verfahren zur Herstellung von Acylcyaniden
DE2708184B2 (de) Verfahren zur Herstellung von a -Ketocarbonsäureamiden (A)
AT359210B (de) Verfahren zur herstellung von desoxyvincamin- amiden
DE3347526A1 (de) Verfahren zur herstellung substituierter chinazolin-2.4(1h.3h)-dione
DE1493965C (de) Verfahren zum Herstellen von Racema ten optisch aktiver Nitrile

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20021028

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

AX Request for extension of the european patent

Free format text: AL;LT;LV;MK;RO;SI

RIN1 Information on inventor provided before grant (corrected)

Inventor name: HOEPFNER, THOMAS

Inventor name: BEHRE, HORST

Inventor name: RODEFELD, LARS

Inventor name: KLAUSENER, ALEXANDER

RIN1 Information on inventor provided before grant (corrected)

Inventor name: HOEPFNER, THOMAS

Inventor name: RODEFELD, LARS

Inventor name: BEHRE, HORST

Inventor name: KLAUSENER, ALEXANDER

17Q First examination report despatched

Effective date: 20030623

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: BAYER CHEMICALS AG

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20040811

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20040811

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20040811

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

Ref country code: CH

Ref legal event code: NV

Representative=s name: E. BLUM & CO. PATENTANWAELTE

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: GERMAN

REF Corresponds to:

Ref document number: 50103229

Country of ref document: DE

Date of ref document: 20040916

Kind code of ref document: P

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20041111

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20041111

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20041111

GBT Gb: translation of ep patent filed (gb section 77(6)(a)/1977)

Effective date: 20041125

LTIE Lt: invalidation of european patent or patent extension

Effective date: 20040811

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20050315

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050315

REG Reference to a national code

Ref country code: IE

Ref legal event code: FD4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050331

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2227193

Country of ref document: ES

Kind code of ref document: T3

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

ET Fr: translation filed
26N No opposition filed

Effective date: 20050512

REG Reference to a national code

Ref country code: GB

Ref legal event code: 732E

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20070314

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 20070417

Year of fee payment: 7

NLS Nl: assignments of ep-patents

Owner name: LANXESS DEUTSCHLAND GMBH

Effective date: 20070305

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 20070514

Year of fee payment: 7

REG Reference to a national code

Ref country code: CH

Ref legal event code: PUE

Owner name: LANXESS DEUTSCHLAND GMBH

Free format text: BAYER CHEMICALS AG# #51368 LEVERKUSEN (DE) -TRANSFER TO- LANXESS DEUTSCHLAND GMBH# #51369 LEVERKUSEN (DE)

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050111

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IT

Payment date: 20070516

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20070308

Year of fee payment: 7

BERE Be: lapsed

Owner name: *LANXESS DEUTSCHLAND G.M.B.H.

Effective date: 20080331

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20080315

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

Effective date: 20081125

REG Reference to a national code

Ref country code: FR

Ref legal event code: TP

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20080331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20080331

REG Reference to a national code

Ref country code: ES

Ref legal event code: FD2A

Effective date: 20080317

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20080315

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20080317

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20080315

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 20110314

Year of fee payment: 11

Ref country code: AT

Payment date: 20110228

Year of fee payment: 11

Ref country code: NL

Payment date: 20110317

Year of fee payment: 11

REG Reference to a national code

Ref country code: NL

Ref legal event code: V1

Effective date: 20121001

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: AT

Ref legal event code: MM01

Ref document number: 273270

Country of ref document: AT

Kind code of ref document: T

Effective date: 20120315

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120331

Ref country code: AT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120315

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20121001

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20130314

Year of fee payment: 13

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 50103229

Country of ref document: DE

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 50103229

Country of ref document: DE

Effective date: 20141001

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20141001